Chromatin state dynamics during blood formation

David Lara-Astiaso, Assaf Weiner, Erika Lorenzo-Vivas, Irina Zaretsky, Diego Adhemar Jaitin, Eyal David, Hadas Keren-Shaul, Alexander Mildner, Deborah Winter, Steffen Jung, Nir Friedman*, Ido Amit

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

582 Scopus citations

Abstract

Chromatin modifications are crucial for development, yet little is known about their dynamics during differentiation. Hematopoiesis provides a well-defined model to study chromatin state dynamics; however, technical limitations impede profiling of homogeneous differentiation intermediates. We developed a high-sensitivity indexing-first chromatin immunoprecipitation approach to profile the dynamics of four chromatin modifications across 16 stages of hematopoietic differentiation. We identify 48,415 enhancer regions and characterize their dynamics.We find that lineage commitment involves de novo establishment of 17,035 lineage-specific enhancers. These enhancer repertoire expansions foreshadow transcriptional programs in differentiated cells. Combining our enhancer catalog with gene expression profiles, we elucidate the transcription factor network controlling chromatin dynamics and lineage specification in hematopoiesis. Together, our results provide a comprehensive model of chromatin dynamics during development.

Original languageAmerican English
Pages (from-to)943-949
Number of pages7
JournalScience
Volume345
Issue number6199
DOIs
StatePublished - 22 Aug 2014

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